The unusually high production of lactate was the earliest and mot outstanding biochemical characteristic discovered in cancerous tissues. It appears that pyruvate serves as the chief hydrogen acceptor for neoplastic tissues, whereas oxygen is the chief hydrogen acceptor in normal tissues. This raises the possibility that the reaction catalyzed by lactic dehydrogenase is essential in neoplastic tissues, but not in other normal resting tissues. Previous attempts by Busch and coworkers and Colowick and coworkers to develop lactic dehydrogenase inhibitors and use them as anti-cancer agents have met with some success, but problems of toxicity and lack of specificity of the agents developed have largely negated their usefulness. Work in my laboratory has led to the discovery of a large family of phenolic compounds which are extremely potent, specific, non-toxic inhibitors of lactic dehydrogenase, and we have synthesized additional structural analogues which possess the same characteristic and, in some cases, surpass the natural products in potency. Preliminary tests have shown pronounced inhibition of Sarcoma 180. One aspect of the proposed research involves further detailed studies of the ability of these compounds to inhibit cancer growth. A second aspect of the proposed research will be aimed at determining whether the metabolic control characteristics and catalytic properties of isolated, pure glycolytic enzymes are altered in tumor cells. These studies will focus on the key control enzymes: (1) protein kinase, (2) phosphofructokinase, and (3) glyceraldehyde phosphate dehydrogenase. Studies will also be made of the patterns of glycolytic isozymes in cancer cells.